Combinatory in vitro effects of the? 32-agonists salbutamol and formoterol in skeletal muscle cells

f32-agonists are used for the treatment of bronchoconstriction, but also abused in doping. Beside an ergogenic activity f32-agonists may have also anabolic activity. Therefore, we investigated the anabolic activity and asso-ciated molecular mechanisms of Salbutamol (SAL) and Formoterol (FOR) alone, as well as in combination in C2C12 myotubes. In differentiated C2C12 cells, dose-dependent effects of SAL and FOR (alone/in combination) on myotube diameter, myosin heavy chain (MHC) protein expression and the mRNA expression of genes involved in hypertrophy were analyzed. f32-adrenoceptor 2 (ADRB2), androgen receptor (AR) and estrogen receptor (ER) inhibitors, as well as dexamethasone (Dexa) were co-incubated with the f32-agonists and myotube diameter was determined. SAL and FOR treatment significantly induced hypertrophy and increased MHC expression and the mRNA expression of Igf1, mTOR, PIk3r1 and AMpKa2. In contrast to an ER inhibitor, the ADRB2 and AR in-hibitors, as well as Dexa antagonized FOR and SAL induced hypertrophy. Combined treatment with SAL and FOR resulted in significant additive effects on myotube diameter and MHC expression. Future clinical studies are needed to prove this effect in humans and to evaluate this finding with respect to antidoping regulations.

Automated summary

This study investigated the anabolic activity and associated molecular mechanisms of Salbutamol (SAL) and Formoterol (FOR) in C2C12 myotubes. Results showed that SAL and FOR induced hypertrophy and increased the expression of myosin heavy chain (MHC) and genes involved in hypertrophy. The ADRB2 and AR inhibitors, as well as dexamethasone, antagonized the hypertrophic effect of FOR and SAL, while the combination of SAL and FOR had an additive effect. Future clinical studies are needed to confirm these findings and evaluate their implications in doping regulations.